Parasitic nematodes infect over half the world's population, resulting in significant morbidity and mortality. Characterization of nematode genomes provides fundamental molecular information about these parasites accelerating basic research and development of new diagnostics and therapeutics. Washington University's Genome Center has generated and made public over 400,000 cDNAs from 30 parasitic species, sequenced 4 genomes to draft coverage with ten more underway including representatives of the major human parasitic groups. The three aims in this proposal analyze the expanding nematode sequences to substantially improve understanding of parasitic nematode biology and cellular pathways. First, we will develop and use bioinformatic tools to process, assemble, and annotate incoming data from all sequencing platforms. These genomic resources will also be disseminated to the wider research community through the centralized parasitic nematode database, Nematode.net. Second, analysis will focus on biochemical pathways conserved and/or taxonomically restricted including proteins that may prove useful as drug targets. Third, we will study the nature and implications of nematode-specific insertions and deletions in proteins involved in environmental information processing and endocrine system. The expected outcome will facilitate and promote the discovery and development of novel interventions to control these important parasites and reduced their associated morbidity and mortality. PUBLIC HEALTH RELEVANCE: The continued development of molecular information, bioinformatics tools, and reagents for the study of parasitic nematodes is crucial, as they infect over half of the world's population and are a leading cause of human morbidity. The main goal of this project is to implement comparative genomics approaches to study the biology and cellular pathways of these important parasites, which on a long run will contribute to improved diagnostics, vaccines, and anthelmintic drugs for broad parasite control.